title: PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice.
abstract: OBJECTIVE
  Peptide YY (PYY3-36) and pancreatic polypeptide (PP) potently inhibit food intake in rodents and humans, however, it is unclear whether they have any synergistic/additive interaction in decreasing food intake.
  
  
  METHODS
  Fasted WT, Y2(-) (/) (-) , Y4(-) (/) (-) , or Y2Y4(-) (/) (-) mice were i.p. administrated with saline, PYY3-36, and/or PP.
  
  
  RESULTS
  Combined injection of PYY3-36 and PP reduces food intake in an additive manner was demonstrated in this study. This effect is mediated via Y2 and Y4 receptors, respectively. It was demonstrated that PYY3-36 and PP activate distinct neuronal pathways in the hypothalamus, as demonstrated by immunostaining for c-fos, which shows distinct patterns in response to either hormone. After PYY3-36 injection, neurons in the dorsal aspect of the arcuate nucleus (Arc), paraventricular nucleus, and dorso-medial nucleus of the hypothalamus (DMH) are activated with minimal responses seen in the ventro-medial nucleus of the hypothalamus (VMH) and lateral hypothalamic area (LHA) of WT mice. These effects are absent in Y2(-) (/) (-) mice. PP activates preferably the lateral aspect of the Arc, the DMH, VMH, and LHA in a Y4 receptor-dependent manner. Importantly, the expression pattern of c-fos immunoreactive neurons induced by combined treatment appears to be the sum of the effects of single treatments rather than a result of synergistic interaction.
  
  
  CONCLUSIONS
  These findings demonstrate that PYY3-36 and PP activate distinct pathways in the hypothalamus to reduce food intake in an additive manner.
authors.affiliation: Neuroscience Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Yan-Chuan
authors.initials: YC
authors.lastname: Shi
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lin
authors.forename: Jackie
authors.initials: J
authors.lastname: Lau
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yagi
authors.forename: Isabella
authors.initials: I
authors.lastname: Kanzler
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D005215:Fasting; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000008:administration & dosage*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D019894:Peptide YY / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36); C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide